Anti-metastatic action of non-steroidal anti-inflammatory drugs.
Epidemiological studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of several types of human cancer. However, the molecular mechanisms by which NSAIDs exert their chemopreventive and anticancer effects are not fully understood. Cyclooxygenase 1 (COX-1) and COX-2 are the main targets for NSAIDs. Recent studies demonstrate that COX-2 is overexpressed in many human cancers and may promote tumorigenesis via: (1) stimulation of cancer cell proliferation; (2) increase of tumor angiogenesis; (3) prevention of cancer cell apoptosis; (4) modulation of immunoregulatory reactions; and (5) enhancement of tumor metastasis. NSAIDs may target the signaling molecules (from upstream activators to downstream effectors) involved in these mechanisms to attenuate the development and progression of cancer. In this review, we discuss the recent findings with regard to the mechanisms by which NSAIDs inhibit tumorigenesis and will specifically focus on the elucidation of NSAID-induced inhibition of tumor metastasis.
Hung
Wen-Chun
WC
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. hung1228@ms10.hinet.net
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases